PRESENTED BY DR CM VARMA AT UPCSI 2018 VARANASI

1. Approach To
Resistant Hypertension

2. HYPERTENSION
IN
INDIA
Anchala et al, J Hypertension 2014

3. Armamentarium for HTN
NICE 2004

4. RESISTANT HYPERTENSION
• Uncontrolled (>140/90 mm Hg)
• office BP
• Despite three antihypertensive drugs
• In adequate doses and combinations
• OR Controlled with 4 drugs
• Including one diuretic
• Long acting: Chlorthalidone/ spiranolactone
• After 3 months follow up
Calhoun et al. AHA/ACC. J Hypertension 2008

5. Magnitude of the problem
10% of HTN are resistant

6. CAVEATS OF DEFINITION
• Secondary causes?
• What is ‘controlled’ BP?
• OBP/ ABP/ HBP?
• Accurate Measurements?
• Which Anti-hypertensives?
• what doses?
• Which diuretics?
• Adherence?

7. SECONDARY HYPERTENSION
Faselis et al, Int J of HTN 2011

8. SPRINT
SPRINT Research Group. NEJM 2015

9. NEW GOALS: AHA ACC 2017

10. RESISTANT HYPERTENSION:
DO NOT TRUST OFFICE BP
ABPM MANDATORY. NICE 2014
Drawz et al. Am J Kidney Dis 2014

11. SPRECTRUM OF
RESISTANT HYPERTENSION
Muxfeldt et al. Hypertension Research 2013

12. Resistant HTN 12.2% True Resistant HTN 7.5%
Sierra et al. Hypertension. 2011
WHO ARE GOING TO HAVE
TRULY RESISTANT HYPERTENSION?

13. Muxfeldt et al. Hypertension Research 2013
RRESISTANT HTN
473
OFFICE BP<140/90
94 (20%)
OFFICE BP>140/90
379 (80%)
SUSTAINED CONTROLLED BP
58 (62%)
MASKED HTN
36 (38%)
TRUE RHTN
226 (60%)
WHITE COAT HTN
153 (40%)
5 years of follow-up
ABPM
LONG TERM FOLLOW UP

14. ABPM: NEW TOOL IN BOX
Muxfeldt et al. Hypertension Research 2013

15. ABPM
• ABPM is a very important tool not only for
diagnosis but also for treatment and follow
up.
• Office BP has a poor prognostic value than
ABPM
Muxfeldt et al. Hypertension Research 2013

16. J HOME STUDY
(n=528)
17.8%
16.1%
23.5%
42.6%
High cholesterol
Female
Low BMI
CAD
Alcohol
Obesity
HCTZ
RESISTANT HTN
Home Blood Pressure
Obara et al. J Hum Hypertens. 2008

17. NICE Pathway
NICE 2011

18. Inaccuracy of BP measurement
Triage BP technique overestimated the prevalence of
uncontrolled RHTN in approximately 33% of the patients
Bhatt et al. J Am Soc Hypertens 2016

19. Adherence Factor
Durand et al. Journal of Hypertension 2017
Adherence method Prevalence
Prescription refill 31%
Serum drug level 86%
Pill counts 3%
24 studies. 68000 patients

20. Inadequate Therapy
44684 patients of resistant HTN
on 3 or more antihypertensive agents
Egan et al. Hypertension 2012
Inadequate Therapy Prevalence
Optimal diuretic 15%
Recommended
optimal dose
50%
Optimal BP therapy in
-Black
-CKD
-DM
-CAD

21. Dosages of anti-hypertensives
Johnston. Drugs 47 (4): 567-575, 1994

22. One antihypertensive at night-time
Harmida et al. Hypertension 2010. (n=250)
Group of single morning dose:
-nondipping pattern twofold higher
-lower nocturnal fall of SBP and DBP
1306 true resistant hypertensives,
those using at least one drug at bedtime:
Better contol of ABP
Better metabolic profile
Less subclinical organ damage
Muxfeldt et al. J Hypertens 2008.

23. Psuedo-Resistant HTN
50-50
Bhatt et al. J Am Soc Hypertens 2016
de la Sierra et al. Hypertension. 2011

24. Profile of Pseudo-resistant HTN
Grigoryan et al. J Clin Hypertens 2013
Parameters Prevalence
White coat HTN 22%
Non Adherent 29%
True resistant 49%
Thiazide, frusemide 91%
Chlorthalidone 0%
Spiranolactone 0%
CCB max dose 15%
ACEI/ARB max dose 40%

25. Primary Hyperaldosteronaemia
PFK score: U pH>7, Female Sex, K<3.5
Yamashita et al. Journal of Hypertension 2017

26. NICE Pathway (cont.)
NICE 2015

27. PATHWAY 2
Home monitoring to exclude white coat HTN
Directly observed therapy to ensure adherence
Patients with eGFR <45 mL/min were excluded
Included predominantly white Caucasians
Williams et al, PATHWAY 2, Lancet 2015

28. Spironolactone was the most effective blood pressure-lowering agent
throughout the distribution of baseline plasma renin
but it was particularly effective in patients with lower renin
Williams et al, PATHWAY 2, Lancet 2015

29. PATHWAY 3
Brown et al. PATHWAY 3. Lancet 2016

30. OGTT
HBP
K
Combination of Amiloride-with-HCTZ was
neutral for glucose and K+ and
reduced BP by 3.4 mmHg more than twice the dose of each single diuretic

31. Chlorthalidone
Pareek et al. J Am Coll Cardiol. 2016

32. White Coat
HTN 15%
Masked
HTN 25%
True Resistant
HTN 45%
Controlled
HTN 15%
Outcome
Daughtery et al. Circulation 2012
White coat HTN not so benign

33. ‘’Refractory’’ hypertension
Refractory hypertension was defined as failure to
achieve blood pressure control with treatment
prescribed by hypertension experts at minimum of 3
follow-up visits during at least 6 months of care,
receiving an 5 or more different antihypertensive
medications.
Acelajado et al. J Clin Hypertens 2012. University of Alabama at Birmingham Hypertension Clinic

34. Study Population
(Resistant HTN)
Definition of RfH % of RfH
Acelajado et al,
2012
retrospective analysis
304 patients
University of Alabama at
Birmingham Hypertension Clinic
>5 drugs
10%
Dudenbostel et
al, 2015
700 patients
Prospective analysis
University of Alabama at
Birmingham
>5 drugs including,
chlorthalidone and
spironolactone 4%
Modolo et al,
2015
116 patients
cross-sectional analysis
>5 drugs
All of the refractory patients
were receiving a diuretic and
most were receiving
spironolactone (76%).
31%
Calhoun et al,
2014
REGARDS study n=30239
community-based cohort
>5 drugs
Diuretic use, including
specifically chlorthalidone and
spironolactone, was not
required as part of the definition
3.6%
Prevalence of Refractory HTN

35. Classification of HTN
As per number of drugs
Dudenbosten et al. Hypertension 2016

36. ‘’Refractory’’
hypertension:
Novel phenotype
Armario et al. J Am Heart Assoc. 2017
Dudenbostel et al. J Nat Sci 2017
Risers are more common

37. Resistant vs Refractory HTN
Resistant HTN
• Fluid dependent
• Low renin
• BNP high
Refractory HTN
• Not fluid dependent
• High sympathetic tone
• BNP low
Dudenbostel et al. J Nat Sci 2017

38. RENAL ARTREY DENERVATION
Bhat et al, BioMed Research International 2015

39. Response of Renal artrey denervation
Favourable response in:
High SBP (≥180 mm Hg), age <65 years, eGFR ≥60 mL/min/ m2
Bhat et al, BioMed Research International 2015

40. Baroreceptor Activation Therapy
Rheos Pivotal Trial
• 265 patients with resistant
hypertension underwent
surgical implantation.
• One month after surgery,
patients were randomly
assigned to have BAT turned
on immediately or to have
BAT turned on six months
later.
• The patients were followed
for at least 12 months
Bakris et al. J of Am Soc of HTN 2012

41. RHEOS PIVOTAL
6 months
Patients receiving BAT
• Had a nonsignificantly larger
decrease in systolic pressure
• Significantly more likely to
achieve a goal systolic
pressure of 140 mmHg.
12 months
• Mean reduction in systolic
pressure in the BAT group
was 25 mmHg
• More than 80 % of these
patients had at least a 10
mmHg decrease in systolic
pressure
Within one month of surgery
35 % of patients had serious adverse effects
including facial nerve injury
Bakris et al. J of Am Soc of HTN 2012

42. Central arteriovenous anastomosis
Late ipsilateral venous stenosis in 29% patients
ROX CONTROL HTN
Lobo et al. Hypertension. 2017

43. Take Home Messages
• ABPM mandatory for diagnosis and follow up.
• HBPM is also suitable. Limitation is night-time BP.
• One BP lowering drug at night time.
• White Coat HTN is not benign.
• Rule out secondary causes. OSA is commonest.
• PFK score to decide utilization of Spiranolactone

44. Take Home Messages (Cont.)
• Pseudo-resistance is 50%. Ensure 3A: accuracy,
adherence, adequacy. Rule out NSAIDS/ OCP.
• Chlorthalidone to start with. Add Spiranolactone
when resistant. Ameloride+HCTZ is reasonable.
• >5 drugs: Refractory HTN. High sympathetic activity.
Thank You